Background/Purpose: Central nervous system involvement is one of the most serious complications in Behçetfs disease (BD). This condition is referred to as neuro-BD (NB) and can be classified into acute type (ANB) and chronic progressive type (CPNB) based upon differences in the clinical course and responses to corticosteroid treatment. It has been well appreciated that Human Leukocyte Antigen (HLA)-B51 is significantly associated with BD. Of note, HLA-B51 has been found in >80% of patients with CPNB. Thus, genetic factors, such as Major Histocompatibility Complex (MHC), have been implicated in the pathogenesis of CPNB. However, there have been no reports on MHC class II antigen in CPNB. The current studies were carried out to examine whether there is any association of MHC class II antigen in CPNB.

Methods: Forty Japanese BD patients meeting the International Criteria for Behçet’s Disease (ICBD) were enrolled for analysis, including 11 patients with ANB and 15 patients with CPNB. Since CPNB has high positivity for HLA-B51, 14 patients of HLA-B51-positive non-NB were included as a control group. The diagnosis of ANB and CPNB was performed according to the diagnostic criteria proposed by the Japanese research committee for BD (Mod Rheumatol (2012) 22:405–413). The genotype determination of HLA-DR was performed using peripheral blood by polymerase chain reaction (PCR)-sequence based typing.

Results: The HLA-B51-positive rate was 36.4% in ANB (4/11), 86.7% in CPNB (13/15), and 100% in non-NB (14/14). HLA-DRB1*0901 were found in 9.1%, 66.7%, and 4.3% of ANB, CPNB and non-NB HLA-B51 positive control, respectively. The relative risk and odds ratio of ANB and CPNB due to the presence of HLA-DRB1*0901 was 2.727 (Fisherfs exact test: p=0.0052) and 20.0 (95% confidence interval (CI): 1.966 to 203.4), respectively. The relative risk and odds ratio of CPNB and HLA-B51-positive non-NB due to the presence of HLA-DRB1*0901 was 2.833 (Fisherfs exact test: p=0.0078) and 12.0 (95% CI: 1.901 to 75.75), respectively. The results of HLA-DR genotyping are shown in Table.

Conclusion: These results disclosed that HLA-DRB1*0901 is significantly associated with CPNB. Moreover, the data suggest that HLA-B51 as well as HLA DRB1*0901 might be involved in the pathogenesis of CPNB possibly continuing production of interleukin (IL)-6.